Molecular Medicine

, Volume 21, Issue 1, pp 337–345 | Cite as

Interleukin-37 Expression Is Increased in Chronic HIV-1-Infected Individuals and Is Associated with Inflammation and the Size of the Total Viral Reservoir

  • Jesper F. Højen
  • Thomas A. Rasmussen
  • Karen Lise D. Andersen
  • Anni A. Winckelmann
  • Rune R. Laursen
  • Jesper D. Gunst
  • Holger J. Møller
  • Mayumi Fujita
  • Lars Østergaard
  • Ole S. Søgaard
  • Charles A. Dinarello
  • Martin Tolstrup
Research Article


Interleukin-37 (IL-37) is a recently identified cytokine with potent antiinflammatory and immunosuppressive functions. The objective of this study was to compare levels of IL-37 mRNA in immunological subgroups of chronic human immunodeficiency virus-1 (HlV-1)-infected individuals and noninfected controls, to determine IL-37’s association with biomarkers of inflammation and reservoir size. This was a cross-sectional study. The HIV-1-infected patients were categorized in three subgroups depending on their combination antiretroviral therapy (cART) treatment status and CD4+ T-cell count. Quantitative RT-PCR was used for the detection of IL-37 mRNA and HIV-1 DNA in peripheral blood mononuclear cells (PBMCs). Biomarkers in plasma were quantified by enzyme-linked immunosorbent assay (ELISA), whereas T-cell activation was determined by flow cytometry. Lastly, lipopolysaccharide (LPS) stimulations of patients PBMCs were carried out to determine differences in IL-37 mRNA response between the subgroups. Sixty HIV-1-infected patients and 20 noninfected controls were included in the study. Steady-state IL-37 mRNA levels in PBMCs were significantly higher in HIV-1-infected individuals compared with noninfected controls: 2.4-fold (p ≤ 0.01) cART-naïve subjects; 3.9-fold (p ≤ 0.0001) inadequate immunological responders; and 4.0-fold (p ≤ 0.0001) in immunological responders compared with noninfected controls. Additionally, levels of the monocyte inflammatory marker sCD14 correlated with IL-37 mRNA (p = 0.03), whereas there was no association with T-cell activation. Finally, we observed a significant correlation between total viral HIV-1 DNA and IL-37 mRNA in PBMCs (p < 0.0001). Collectively, our data shows that the level of IL-37 mRNA is affected by chronic HIV-1-infection. A relationship with the activation of the monocyte compartment is suggested by the correlation with sCD14 and, interestingly, IL-37 could be related to the size of the total viral HIV-1 reservoir.



We would like to acknowledge all the participating patients who made this study possible. Special gratitude is also extended for Lene Svinth Jøhnke and Erik Hagen for their help and guidance in the lab, and to the medical laboratory assistants in Q-lab. The work was supported by The Danish Research Council (FSS) by grant 0602-02300B to M Tolstrup and by the Augustinusfonden, Familien Hede Nielsens Fund and Ulla og Mogens Folmer Andersens Fund to JF Højen.

Supplementary material

10020_2015_2101337_MOESM1_ESM.pdf (318 kb)
Supplementary material, approximately 318 KB.


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Authors and Affiliations

  • Jesper F. Højen
    • 1
  • Thomas A. Rasmussen
    • 1
  • Karen Lise D. Andersen
    • 1
  • Anni A. Winckelmann
    • 1
  • Rune R. Laursen
    • 1
  • Jesper D. Gunst
    • 1
  • Holger J. Møller
    • 2
  • Mayumi Fujita
    • 3
  • Lars Østergaard
    • 1
  • Ole S. Søgaard
    • 1
  • Charles A. Dinarello
    • 4
    • 5
  • Martin Tolstrup
    • 1
  1. 1.Department of Infectious DiseasesAarhus University HospitalAarhus NDenmark
  2. 2.Department of Clinical BiochemistryAarhus University HospitalAarhusDenmark
  3. 3.Department of DermatologyUniversity of Colorado DenverAuroraUSA
  4. 4.Division of Infectious DiseasesUniversity of Colorado DenverAuroraUSA
  5. 5.Department of MedicineRadboud University Medical CentreNijmegenThe Netherlands

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